Recently, researchers and clinicians have focused increased attention on a group of children with severe mood and behavioral dysregulation. These children are characterized by impairing symptoms that include abnormal baseline mood (i.e. irritability, anger, and/or sadness), hyperarousal (e.g. insomnia, agitation, distractibility), and increased reactivity to negative emotional stimuli. Because this syndrome shares many clinical features with bipolar disorder (BPD), there is considerable debate as to whether these children should be diagnosed with BPD. However, children with this syndrome lack the cardinal symptoms of BPD, and other DSM-IV diagnoses (ADHD, ODD, etc.) capture heterogeneous clinical populations that include many children who do not exhibit the symptoms noted above. Therefore, the goals of this project are 1) to identify reliably a group of children with severe mood and behavioral dysregulation in order to characterize them clinically and follow them longitudinally; 2) to conduct a double-blinded, placebo-controlled trial of lithium in this population; and 3) investigate whether lithium response, which has been associated with neurotrophic effects and with changes in phosphoinositide signaling in bipolar patients, has similar effects in this group of patients. Standardized interview modules and rating scales will be used to rate the clinical features of mood dysregulation. A double-blind, placebo-controlled trial of lithium will be conducted, and magnetic resonance spectroscopy (MRS) to measure NAA and mI will be preformed before and after treatment. Approximately 10 patients have completed the treatment trial, and MRS scans have been obtained. In addition, MRS scans and neuropsychological test data are being acquired from a sample of control adults and children to allow us to establish developmental norms for neurochemistry, and to explore associations between NAA levels and tests of prefrontal cortical function. Finally, a collaboration with Children's National Medical Center has been established in order to allow us to apply, in the setting of a tertiary care child psychiatric clinic, standardized instruments designed to characterize children with severe mood dysregulation.